For a long period of time after the finding by Donne in 1842 (see C.R. Acad. Sci. (Paris), 14, 336-368, 1842); blood platelets have been considered as the component in blood which is necessary for hemostasis. At present, it has been clarified that blood platelets not only play the principal part in the hemostatic mechanism of blood but also are multi-functional as participating in the creation of arteriosclerosis, cardiovascular system disorders including thrombotic disorders, cancer metastases, inflammations, rejections after transplants, and also immunoreactions, etc., which are clinically important. The thrombotic disorders and ischemic disorders are therapeutically treated by restoring the circulation of the blood by the application of medicines or by physical means. However, a clinically problematic phenomena has been found recently that, after the restoration of the blood circulation, the activation, the adhesion and the aggregation of blood platelets are promoted based on the damage of the blood vessel tissue including endothelial cells and the unbalanced systemic fibrinolysis-coagulation equilibrium caused by the medicines itself, and the like. For instance, it has been clarified that, after the circulation of the blood has been restored by thrombolytic therapy using t-PA (tissue Plasminogen Actitor) or the like, the fibrinolytic activity and the coagulating activity are activated to break the systemic fibrinolysis-coagulation equilibrium. Clinically, it causes re-occlusion and is therefore seriously problematic in the therapy (see J. Am. Coll. Cardiol., 12, 616-623, 1988). On the other hand, a PTCA Percutaneous transluminal coronary angioplasty) therapy has been rapidly popularized, with producing good results in some degree, for curing disorders as based on coronary stenosis and aortostenosis, such as stenocardia, myocardial infarction, etc. However, this therapy involves serious problems in that it damages the blood vessel tissue including endothelial cells to cause acute coronary obstruction and even re-stenosis which occurs in about 30% of therapeutical cases. Blood platelets play the principal role in various thrombotic disorders (e.g., re-occlusion) following such blood circulation-restoring therapy. Therefore, the effectiveness of anti-platelet agents would be expected for such disorders. However, conventional anti-platelet agents have not as yet been verified to be satisfactorily effective. GPIIb/IIIa is a platelet membrane glycoprotein which is one of the integrin family (see Blood, 80, 1386-1404, 1992). This integrin binds to adhesive proteins such as fibrinogen, von Willebrand factor, etc., and have an important function at the terminal in blood platelet aggregation. Monoclonal antibodies against GPIIb/IIIa, peptides having an RGD sequence and the like have potent platelet aggregation inhibiting activity, and some of which have already been put into clinical examinations.
Non-peptidic, low molecular weight GPIIb/IIIa antagonists are known in a published Japanese patent application (kokai) 4-288051 (sulfonamide fibrinogen receptor antagonists of the following representative compound, ##STR2## and a published Japanese patent application (kokai) 6-25227 (cyclic imino derivatives of the following representative compound, ##STR3## and are disclosed by Leo et al. (see Journal of Medicinal Chemistry, 35, 4393-4407, 1992) in which the following representative compound is disclosed. ##STR4## The piperizine acetic acid derivatives of the following general formula are disclosed in a published PCT patent application WO093/10091. ##STR5## (in which X.sup.1 and y.sup.1, which may be the same or different, represent CH or N;
X.sup.2 represents CH or, when X.sup.1 represents CH, may also represent N; PA1 y.sup.2 represents N or, when y.sup.1 represents N, may also represent CH; PA1 z represents N or N.sup.+ R.sup.5 ; PA1 R.sup.1 represents a hydrogen atom or a hydroxyl, C.sub.1-4 alkyl or 2,2,2-trifluoroethyl group; PA1 R.sup.2 represents a hydrogen atom or, when both X.sup.1 and X.sup.2 represent CH, may also represent a fluorine, chlorine or bromine atom or a C.sub.1-4 alkyl group; PA1 R.sup.3 represents a hydrogen atom or, when both Y.sup.1 and y.sup.2 represent N, may also represent a C.sub.1-4 alkyl or hydroxymethyl group; PA1 R.sup.4 represents a hydrogen atom or, when Z represents N, R.sup.4 may also represent a C.sub.1-4 alkyl group; PA1 R.sup.5 represents a C.sub.1-4 alkyl or phenyl C.sub.1-4 alkyl group; PA1 R.sup.6 represents a hydrogen atom or a C.sub.1-4 alkyl group.) PA1 X.sup.1 represents a lower alkylene group; PA1 X.sup.2 represents a single bond or a lower alkylene group; PA1 m represents 0, 1, or 2; PA1 n represents 0 or 1, provided that n=1 when m=0.). PA1 R.sup.2 and R.sup.3 : the same or different and each represents a carboxyl group or a group which can be converted into a carboxyl group in vivo; PA1 X.sup.1 and X.sup.2 : the same or different and each represents a lower alkylene group; PA1 m: 0, 1 or 2; PA1 n: 0 or 1, provided that n=1 when m=0. The same applies hereinafter.) PA1 the substituted-amidinobenzene derivatives or salts thereof, wherein the group which can be converted into an amidino group in vivo of R.sup.1 is a group selected from the group consisting of a hydroxyamidino group, a lower alkoxycarbonylamidino group, a lower alkoxyamidino group and a lower alkanoylamidino group; PA1 the substituted-amidinobenzene derivatives or salts thereof, wherein the group which can be converted into an carboxyl group in vivo of R.sup.2 and R.sup.3 is a group selected from the group consisting of a lower alkoxycarbonyl group, a lower alkoxy-lower alkoxycarbonyl group, a lower alkoxy-lower alkoxy-lower alkoxycarbonyl group, a halogeno-lower alkoxylcarbonyl group, a lower alkenyloxycarbonyl group, a lower alkanoyloxy-lower alkoxycarbonyl group, a lower alkenoyloxy-lower alkoxycarbonyl group, a lower alkanoyl-lower alkoxycarbonyl group, a lower alkenoyl-lower alkoxycarbonyl group, a lower alkoxy-lower alkanoyloxy-lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-lower alkoxycarbonyl group, a lower alkoxy-lower alkoxycarbonyloxy-lower alkoxycarbonyl group, di-lower alkylamino-lower alkoxycarbonyl group, a cycloalkyloxycarbonyloxy-lower alkoxycarbonyl group, a lower alkoxybenzyloxycarbonyl group, a nitrobenzyloxycarbonyl group, a lower alkoxybenzhydryloxycarbonyl group, a benzhydryloxycarbonyl group, a benzoyloxy-lower alkoxycarbonyl group, a 2-oxotetrahydrofuran-5-yloxycarbonyl group, a 2-oxo-5-alkyl-1,3-dioxolen-4-ylmethoxycarbonyl group, a tetrahydrofuranylcarbonyloxymethoxycarbonyl group, and a 3-phthalidyloxycarbonl group; and PA1 1) When Y.sup.2 is Y.sup.1 and A.sup.2 is a methylene group in the compound (XV) above, the reaction is carried out in the similar manner as described in 1) of Production Process C. PA1 2) When Y.sup.2 is Y.sup.1 and A.sup.2 is a carbonyl group in the compound (XV) above, the reaction is carried out in the similar manner as described in 2) of Production Process C. PA1 3) When Y.sup.2 is a hydrogen atom and A.sup.2 is a carbonyl group in the compound (XV) above, the reaction is carried out in the similar manner as described in 3) of Production Process C.
However, the compounds in the above application is disclosed as platelet aggregation inhibitor. GPIIb/IIIa antagonists having wide safety range and a definite effect through oral administration are highly desired.